Project 1 has the overall theme of studying the immuno-genetic epidemiology of complex malaria in India as part ofthe Center for the Study of Complex Malaria in India. Single-species infections by a malaria parasite, 'successive' (one after another) infections, mixed-species (two or more concurrent) infections, and mixed-genotype infections will be detected during a 5 year longitudinal study at three eco-epidemiologically different field stations in India, and used in four sub-Projects. Sub-Project 1 will investigate the development of natural immunity to malaria in individuals: its association with prior exposure to malaria, parasite species, and parasite genetic diversity. Sub-Project 1 will also study complex mixed-species infections, and the differing ratios of Plasmodium species in infections across geography and time. Sub-Project 2 will determine the genetic diversity ofthe highly variable